sFlt-1:PlGF Complex Detection for Preeclampsia Diagnosis

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Solution Overview

Problem

Current methods are inadequate for early diagnosis and monitoring of preeclampsia, a condition that poses significant risks to both maternal and fetal health, as they rely on clinical evaluations that are ineffective for early detection and do not account for the imbalance of circulating angiogenic factors that precede clinical manifestations.

Innovation Solution

A method and composition for determining the presence or amount of the sFlt-1:PlGF complex using capture and detector agents that bind specifically to these molecules, allowing for the detection and quantification of the complex in a sample, which can guide therapy, prediction, detection, or monitoring of preeclampsia and related diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If clinical evaluation methods (blood pressure monitoring and urine protein testing) are used for preeclampsia diagnosis, then the diagnosis can be made based on routine procedures, but the diagnosis is ineffective for early detection and only becomes informative after the 20th week of pregnancy

Engineering Contradiction:
Improvediagnosis timingVSAvoiddiagnosis accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent measures sFlt-1 and PlGF levels in maternal serum during the first trimester (before the 20th week) to predict the risk of developing preeclampsia before clinical symptoms appear. This preliminary measurement of biomarkers allows early identification of high-risk patients, enabling preventive interventions before the disease manifests clinically.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If early biomarker measurement is implemented to improve early diagnosis, then early intervention becomes possible, but the complexity of the diagnostic system increases due to requiring specialized immunoassays and biomarker analysis

Engineering Contradiction:
Improveprediction capabilityVSAvoidassay complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a multiplex immunoassay system that can simultaneously measure multiple biomarkers (sFlt-1, PlGF, and other angiogenic factors) in a single test using maternal serum samples. This multi-functional approach increases predictive reliability by considering multiple disease mechanisms at once, while the automated nature of the assay reduces operational complexity compared to performing multiple separate tests.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If sFlt-1 and PlGF levels are measured to detect the sFlt-1:PlGF complex, then early prediction of preeclampsia is enabled, but the measurement precision requirements increase due to the need to detect complex formation and distinguish from free proteins

Engineering Contradiction:
Improvecomplex detection accuracyVSAvoidcomplex quantification
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses specific antibodies as intermediary reagents that recognize and bind to the sFlt-1:PlGF complex formation. These antibodies serve as mediators that translate the molecular interaction into a measurable signal, allowing indirect but accurate detection of complex formation. The assay system includes capture antibodies and detection antibodies that work together to specifically identify the complex rather than free proteins, enabling precise measurement of the pathological interaction.

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables early identification of preeclampsia by quantifying the sFlt-1:PlGF complex, providing valuable insights for clinicians to intervene early and reduce the risk of complications, with demonstrated utility in distinguishing between normal and preeclampsia patient samples through immunoassays and mathematical transformations.

Implementation Method 1

capturing the complex with a capture agent that binds to sFlt-1, PlGF, or sFlt-1:PlGF complex

Methodology Applied
Scientific EffectSpecific binding:

Implementation Method 2

detecting the complex with a detector agent that binds to sFlt-1, PlGF, or sFlt-1:PlGF complex

Methodology Applied
Scientific EffectSpecific binding:

Data Source

PatentEP2235529B1Determination of sflt-1:angiogenic factor complex
Publication Date: 2016.12.14 ORTHO CLINICAL DIAGNOSTICS INC
  • EP2235529B1 patent drawingFigure 1~2
  • EP2235529B1 patent drawingFigure 3~4
  • EP2235529B1 patent drawing

AI summary

Methods for determining the presence or amount of a complex comprising a first and second molecular entity are provided, preferably an sFlt-1 : P1GF complex. A determination of the presence or amount of the complex can be used in methods for predicting, detecting, monitoring a disease, or guiding therapy in respect to a disease such as vascular, vascular-related disease, cardiac, cardiac-related disease, cancer, cancer-related disease, preeclampsia, and preeclampsia-related disease. Determining sFlt-1 : angiogenic factor complex is particularly useful for predicting and detecting preeclampsia in early stages of gestation and in stages of the disease where clinical evaluation may be uninformative.